MicroRNA-145 regulates the differentiation of human adipose-derived stem cells to smooth muscle cells via targeting Krüppel-like factor 4

Abstract

Understanding the molecular mechanisms underlying human adipose-derived stem cell (hASC) differentiation to smooth muscle may contribute to the development of effective therapies for relevant muscle defects, such as bladder wall and urethral defects. A previous study described the differentiation of hASCs to smooth muscle cells (SMCs) by transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein‑4 (BMP4) treatment. The present study investigated whether microRNA-145 (miR‑145) may be involved in the process of hASC differentiation. The expression of miR‑145 was significantly increased during differentiation of ASCs to SMCs. SMC‑specific genes and proteins, including a‑smooth muscle actin (α‑SMA), smooth muscle protein‑22α(SM22α), calponin and myosin heavy chain (SM‑MHC) were upregulated by transfection of a miR‑145 mimic. By contrast, these factors were downregulated following introduction of antisense oligonucleotides. In addition, Krüppel‑like factor 4 (KLF4) levels, which decreased during the differentiation of hASCs, were downregulated when the cells were transfected miR‑145 mimics. Futhermore, inhibition of KLF4 by treatment with short‑interfering‑RNA against KLF4, resulted in increased expression of SMC‑specific genes and proteins. In conclusion, the results of the present study demonstrated that by regulating KLF4, miR‑145 may be involved in regulating smooth muscle differentiation of ASCs induced by TGF‑β1 and BMP4.

The role of BMP4 in adipose-derived stem cell differentiation: A minireview

“…Frontiers in Cell and Developmental Biology frontiersin.org of the induction. They also demonstrated that the Krüppel-like factor 4 (KLF4) protein regulated the smooth muscle differentiation that was induced by BMP4 signaling (Aji et al, 2017). Furthermore, Lin et al (2020) revealed that N6-adenosine methyltransferases (Mettl3), an N6-methyltransferase that methylates adenosine residues at the N6 position of some RNAs, was upregulated following BMP4 induction.…”